Neurofilament, but not Alzheimer disease biomarkers in the acute phase correlate with cognitive performance after cardiac arrest

TL;DR

This study found that the biomarker neurofilament light, but not Alzheimer disease markers, correlates with cognitive outcomes after cardiac arrest.

Contribution

The study demonstrates that neurofilament light is a better predictor of cognitive function than Alzheimer disease biomarkers in cardiac arrest survivors.

Findings

Neurofilament light (NfL) showed stronger correlations with cognitive outcomes than Alzheimer disease biomarkers.

Alzheimer disease biomarkers had weak correlations (rho = -0.22 to 0.18) and lower predictive accuracy for cognitive impairment.

NfL had a higher discriminatory ability (AUC 0.66–0.86) compared to Alzheimer disease biomarkers (AUC 0.44–0.68).

Abstract

Biomarkers serve as a quantitative measure of brain injury and may predict cognitive outcome after cardiac arrest. This study investigates the association and predictive accuracy of acute changes in Alzheimer disease-associated biomarkers to cognitive outcome in cardiac arrest survivors.

Retrospective study of the Target Temperature Management after Out-of-Hospital cardiac arrest trial. Serum from adult cardiac arrest survivors was sampled prospectively at 24, 48, and 72 h post-arrest and analyzed for peak-levels of Alzheimer disease markers (p-tau181, total tau, amyloid β [Aβ40 and Aβ42]), and the neurodegenerative biomarker neurofilament light (NfL). Cognitive outcome was evaluated blinded from biomarker results using four performance-based assessments at 6 months post-arrest. Spearman correlations were calculated. Area Under the Receiver Operating Characteristics curves (AUC) were calculated for biomarkers discriminatory ability for binary results of cognitive performance.

206/342 (60 %) survivors from participating sites were included. Median was age 62 (IQR 53–69), 86 % male, 15 (7 %) had Mini-Mental State Examination (MMSE) scores < 24. Alzheimer disease biomarkers exhibited at best small correlations to cognitive outcomes (rho = −0.22 to 0.18). The correlation between outcome instruments and NfL was rho = −0.32 to −0.20 (p < 0.01). Discriminatory ability of cognitive impairment for acute changes in Alzheimer disease biomarkers was AUC 0.44–0.68 (95 % CI 0.29–0.82), and AUC 0.66–0.86 (95 % CI 0.59–0.95) for NfL.

In contrast to tau- and amyloid-related biomarkers, NfL could be more useful for predicting cognitive function in cardiac arrest survivors. Low participation by survivors with severe brain injury may have influenced results.

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